Malignant Hyperthermia (MH) is an autosomal dominant disorder of skeletal muscle[unreadable] that causes a life threatening reaction following administration of commonly used[unreadable] inhalational anesthetics such as halothane, or the depolarizing muscle relaxant[unreadable] succinylcholine. Administration of the anesthetics during surgery causes an altered[unreadable] release of calcium from the sarcoplasmic reticulum (SR) through the ryanodine receptor[unreadable] (RYR1), which in turn induces a cascade of biochemical events that culminates in a[unreadable] nypermetabolic state (fulminant episode) with hyperthermia. If not treated, promptly by[unreadable] withdrawing the anesthetic and administering dantrolene (a drug that inhibits release of[unreadable] Ca++ from the SR) mortality can be as great as 70%. Because most MH individuals[unreadable] appear normal and susceptibility becomes apparent only after exposure to anesthetics,[unreadable] identifying MH susceptible individuals prior to surgery is difficult requiring muscle biopsy[unreadable] and measurements of the contractile sensitivity to RYR1 agonists caffeine and halothane.[unreadable] The caffeine-halothane contracture test (CHCT) phenotypes patients as MHS[unreadable] (susceptible) or MHN (normal). The CHCT has a sensitivity of 93% and specificity of 78%.[unreadable] USUHS has performed over 400 CHCT tests on patients. Approximately 50% of patients[unreadable] are diagnosed CHCT positive. Core C will review MH susceptible individuals, probands[unreadable] and family members for clinical histories of adverse responses to anesthetic drugs,[unreadable] phenotype skeletal muscle samples with performance of a CHCT, and genotype CHCT[unreadable] positive patients for causative mutations in RyR1 and the a1s-DHPR genes. They will[unreadable] collect blood samples from these patients a) for mRNA for use in profiling studies, b) to[unreadable] make permanent B-lymphocyte cell lines for physiologic and transcriptional profiling[unreadable] studies, and c) for the isolation of dendritic cells. In addition, they will collect muscle[unreadable] samples to make myoblast cultures to be purified by Core B, and flash freeze discarded[unreadable] muscle samples for transcriptional profiling studies.